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MiR?204?5p promotes apoptosis and inhibits migration of gastric cancer cells by targeting HER?2.

ABSTRACT: Gastric cancer is one of the most common types of cancer worldwide, with a high incidence and mortality rate. MicroRNAs (miRs) play an important role in tumorigenesis, cell proliferation, migration, apoptosis and metastasis of cancer. The present study aimed to investigate the role and potential mechanism of miR?204?5p in gastric cancer. The mRNA expression levels of miR?204?5p in gastric cancer were determined by reverse transcription?quantitative PCR. Cell proliferation was determined using Cell Counting Kit?8 and colony formation assays. Flow cytometry analysis was performed to detect the cell apoptosis rate. Wound healing and Transwell assays were carried out to determine the cell migration and invasion rates, respectively. A putative binding site of miR?204?5p in the 3' untranslated region of human epidermal growth factor receptor 2 (HER?2) was predicted using a bioinformatics algorithm and confirmed using a dual?luciferase reporter assay. miR?204?5p levels were downregulated in gastric cancer cells. Overexpression of miR?204?5p significantly inhibited cell proliferation and decreased cell colony formation. Additionally, miR?204?5p decreased the migration and invasion rates of gastric cancer cells. Furthermore, an increased apoptotic rate was detected following overexpression of miR?204?5p, along with increased expression levels of Bax and decreased expression levels of Bcl?2. HER?2 was a direct target of miR?204?5p, and inhibition of HER?2 acted as a tumor suppressor by inhibiting cell proliferation, migration and invasion, and promoting cell apoptosis, which was reversed by the inhibition of miR?204?5p expression. These results suggested that miR?204?5p could exert its anti?tumor function by inhibiting cell proliferation, migration and invasion, and promoting cell apoptosis via regulation of HER?2, which may be a potential therapeutic target for gastric cancer.

SUBMITTER: Yang S

PROVIDER: S-EPMC7453524 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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miR‑204‑5p promotes apoptosis and inhibits migration of gastric cancer cells by targeting HER‑2.

Yang Shu S Chen Binni B Zhang Baogen B Li Caiping C Qiu Yuena Y Yang Hanhui H Huang Zhongxin Z

Molecular medicine reports 20200728 4

Gastric cancer is one of the most common types of cancer worldwide, with a high incidence and mortality rate. MicroRNAs (miRs) play an important role in tumorigenesis, cell proliferation, migration, apoptosis and metastasis of cancer. The present study aimed to investigate the role and potential mechanism of miR‑204‑5p in gastric cancer. The mRNA expression levels of miR‑204‑5p in gastric cancer were determined by reverse transcription‑quantitative PCR. Cell proliferation was determined using Ce ...[more]

PMID: 32945425

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Project description:Gastric cancer seriously affects human health and research on gastric cancer is attracting more and more attentions. In recent years, molecular targets have become the research focus. Accumulating evidence indicates that miR-450a-5p plays a critical role in cancer progression. However, the biological role of miR-450a-5p in gastric carcinogenesis remains largely unknown. In this study, we explore the effects and mechanisms of miR-450a-5p on the development and progression of gastric cancer. We used gain-of-function approaches to investigate the role of miR-450a-5p on gastric cancer cell proliferation, migration, invasion, and apoptosis using biological and molecular techniques including real-time quantitative PCR (RT-qPCR), CCK-8, colony formation, flow cytometry, Western blot, wound healing, transwell chamber, dual luciferase reporter, and tumor xenograft mouse model. We found that gastric cancer cells have low expression of miR-450a-5p and overexpression of miR-450a-5p inhibited gastric cancer cell proliferation, migration and invasion, and induced apoptosis in vitro. Moreover, we demonstrated that ectopic expression of miR-450a-5p inhibited gastric cancer growth in vivo. At the molecular level, overexpression of miR-450a-5p significantly increased the expression of pro-apoptotic proteins, including caspase-3, caspase-9, and Bax, and inhibited the expression of anti-apoptotic protein Bcl-2. Luciferase reporter experiment suggested that camp response element binding protein 1 (CREB1) had a negative correlation with miR-450a-5p expression, and knockdown of CREB1 alleviated gastric cancer growth. Furthermore, we also found that miR-450a-5p inhibited the activation of AKT/GSK-3β signaling pathway to inhibit the progression of gastric cancer. Collectively, miR-450a-5p repressed gastric cancer cell proliferation, migration and invasion and induced apoptosis through targeting CREB1 by inhibiting AKT/GSK-3β signaling pathway. MiR-450a-5p could be a novel molecular target for the treatment of gastric cancer.

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MiR?204?5p promotes apoptosis and inhibits migration of gastric cancer cells by targeting HER?2.

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miR‑204‑5p promotes apoptosis and inhibits migration of gastric cancer cells by targeting HER‑2.

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